A Study to Evaluate the Safety and Tolerability of Tirbanibulin Ointment 1% in Adult Participants With Actinic Keratosis

NCT05279131 | Completed Phase 3 Results FDA Drug

• 1 other identifier: M-14867-32
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of the study is to evaluate the safety, tolerability and treatment effect of tirbanibulin ointment 1% when applied to a field of approximately 100 cm\^2 on the face or balding scalp.

Conditions

Keratosis, Actinic

Outcome Measures

Primary Outcomes (24)

• Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 5

  Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 5 were reported.

  Baseline, Day 5

• Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 8

  Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 8 were reported.

  Baseline, Day 8

• Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 15

  Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 15 were reported.

  Baseline, Day 15

• Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 29

  Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 29 were reported.

  Baseline, Day 29

• Number of Participants Categorized by Local Tolerability Score by Visit for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration) at Day 57

  Local tolerability score was evaluated by investigator in terms of presence and absence of erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration signs and its severity in the areas of body where medication was applied. These symptoms were assessed by using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. Number of participants categorized by local tolerability score by visit for each individual signs (erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration) at Day 57 were reported.

  Baseline, Day 57

• Number of Participants With Maximum Local Tolerability Score Post-baseline for Each Individual Signs (Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration)

  Maximum local tolerability score post baseline was defined as the highest grade of any LSR reported at any post-baseline visits for a participant. Local tolerability score was assessed for signs erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration using a 4 - point grade scale of 0 - 3, where a score of 0=absent, 1=mild (slightly, barely perceptible), 2=moderate (distinct presence), and 3=severe (marked, intense). The higher score indicates severe symptoms. If a participant maximum individual sign local tolerability score stayed at 0 throughout the study, the participant was considered censored at last local tolerability score observation. Number of participants with maximum local tolerability score for each individual signs including erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration were reported.

  Baseline, Maximum post-baseline (up to Day 57)

• Time to Maximum Local Tolerability Score for Erythema, Flaking/Scaling, Crusting, Swelling, Vesiculation/Pustulation, and Erosion/Ulceration

  Time to maximum local tolerability score (in days) for each individual sign was calculated as \[Date of first post-baseline occurrence of maximum local tolerability score for this individual sign - Date of first dose\]. If a participant maximum individual sign LTA score stays at 0 throughout the study, the participants was considered censored at their last LTA score observation. Maximum local tolerability score was assessed for each signs using a 4 - point scale of 0 - 3, where 0 = absent, 1= mild, 2= moderate and 3 = severe. The higher score indicates severe symptoms. Time to maximum local tolerability score for erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration was reported.

  Baseline up to Day 57

• Local Tolerability Signs Total Composite Score by Visit at Day 5

  Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score assessed from baseline up to Day 5 was reported.

  Baseline, Day 5

• Local Tolerability Signs Total Composite Score by Visit at Day 8

  Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 8 was reported.

  Baseline, Day 8

• Local Tolerability Signs Total Composite Score by Visit at Day 15

  Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 15 was reported.

  Baseline, Day 15

• Local Tolerability Signs Total Composite Score by Visit at Day 29

  Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 29 was reported.

  Baseline, Day 29

• Local Tolerability Signs Total Composite Score by Visit at Day 57

  Local tolerability signs composite score by visit was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Local tolerability signs total composite score by visit at Day 57 was reported.

  Baseline, Day 57

• Maximum Local Tolerability Signs Total Composite Score Post Baseline

  The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. Maximum local tolerability signs total composite score post baseline was reported.

  Baseline, Maximum post-baseline (up to Day 57)

• Time to Maximum Local Tolerability Total Composite Score

  Time to maximum composite local tolerability score (in days) was calculated as (Date of first post-baseline occurrence of maximum composite local tolerability score - Date of first dose). The maximum local tolerability signs composite score across visits was derived as the maximum local tolerability composite score observed post-baseline. Local tolerability signs composite score was defined as the sum of the scores graded from 0 (absent) to 3 (severe) on all six individual tolerability sign categories - erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration which gave total composite score ranged from 0 to 18. The higher score indicates severe symptoms. If a participant's maximum composite local tolerability score stays at 0 throughout the study, the participant was considered censored at their last local tolerability score observation. Time to maximum local tolerability total composite score was reported.

  Baseline up to Day 57

• Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 5

  Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 5 was reported.

  Baseline, Day 5

• Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 8

  Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 8 was reported.

  Baseline, Day 8

• Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 15

  Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 15 was reported.

  Baseline, Day 15

• Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 29

  Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 29 was reported.

  Baseline, Day 29

• Number of Participants With Pigmentation and Scarring in the Treatment Area by Visit at Day 57

  Absence and presence of pigmentation (i.e., hypopigmentation and hyperpigmentation) and scarring in the treatment field by visit at Day 57 was reported.

  Baseline, Day 57

• Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and Adverse Events of Special Interest (AESIs)

  TEAEs were defined as either those adverse events (AEs) with an onset after dosing or those pre-existing conditions that worsened after dosing. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an Investigational Product. An SAE with any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect in the child of a participant who was exposed to the study drug, or any other medically important event that may jeopardize the patient or require intervention to prevent one of the other outcomes. AESI's included in this study were skin cancers (including basal cell carcinoma, squamous cell carcinoma, and melanoma) based on their relevance for the current intended use. TEAEs included both serious and non-serious AEs.

  Baseline up to Day 57

• Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

  Laboratory parameters included blood chemistry, hamatology, and urinalysis. Clinically significant laboratory abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in laboratory parameters (included hematology, blood chemistry and urinalysis) were reported.

  Baseline up to Day 57

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Vital signs included measurement of pulse rate, systolic and diastolic blood pressure, respiratory rate, and body temperature. Clinically significant vital signs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in vital signs were reported.

  Baseline up to Day 57

• Number of Participants With Clinically Significant Abnormalities in Physical Examination

  Physical examination included weight and height measurements. Clinically significant physical examination abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in physical examination were reported.

  Baseline up to Day 57

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)

  ECG included heart rhythm, heart rate, QRS intervals, QT intervals, RR intervals and corrected QT (QTc) intervals parameters measurement. Clinically significant ECGs abnormalities assessment was based on Investigator interpretation. Number of participants with clinically significant abnormalities in ECG were reported.

  Baseline up to Day 57

Study Arms (1)

Tirbanibulin (Klisyri®)

EXPERIMENTAL

Participants will apply tirbanibulin ointment 1% once daily for 5 days beginning Day 1. Participants will be evaluated for safety, tolerability, and the presence of Actinic Keratosis (AK) lesions in the treatment field (TF) until completion of the response assessment period at Day 57.

Drug: Tirbanibulin ointment 1%

Interventions

Tirbanibulin ointment 1% DRUG

Applied topically for 5 days over a field of approximately 100 cm\^2 on the face or balding scalp with AK.

Tirbanibulin (Klisyri®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Having a treatment field (TF) on the face or balding scalp (excluding lips, eyelids, and inside nostrils and ears) that measures approximately 100 cm\^2 (eg, mid face) and contains 4 to 12 clinically typical, visible, and discrete actinic keratosis (AK) lesions within the TF
• Willing to avoid excessive sunlight or ultraviolet (UV) light exposure, including the use of tanning beds, to the face or scalp during the study
• Ability to understand the purpose and risks of the trial, willingness and ability to comply with the protocol, and provided written informed consent in accordance with institutional and regulatory guidelines

You may not qualify if:

• Presence in the TF of
• Clinically atypical and/or rapidly changing AK lesions in the TF
• Hyperkeratotic or hypertrophic lesions, recalcitrant disease (had cryosurgery on 2 previous occasions) and/or cutaneous horn
• History of invasive squamous cell carcinoma (SCC), Bowen's disease, basal cell carcinoma (BCC), or other malignant tumors in the TF
• Any other dermatological disease that causes difficulty with examination
• Previous treatment with tirbanibulin ointment 1%.
• Anticipated need for inpatient hospitalization or inpatient surgery from Day 1 to Day 57
• Treatment with 5-fluorouracil, imiquimod, ingenol mebutate, diclofenac, photodynamic therapy, or other treatments for AK within the TF or within 2 cm of the TF, within 8 weeks prior to the Screening visit
• Use of systemic retinoids (eg, isotretinoin, acitretin, bexarotene) within 6 months prior to the Screening visit

Sponsors & Collaborators

• Almirall, S.A.: lead

Study Sites (7)

Almirall Investigation Site 7

Hot Springs, Arkansas, 71913, United States

Location

Almirall Investigation Site 6

Encinitas, California, 92024, United States

Location

Almirall Investigation Site 3

Sweetwater, Florida, 33172, United States

Location

Almirall Investigation Site 5

Rolling Meadows, Illinois, 60008, United States

Location

Almirall Investigation Site 4

Austin, Texas, 78759, United States

Location

Almirall Investigational Site 1

College Station, Texas, 77845, United States

Location

Almirall Investigation Site 2

San Antonio, Texas, 78213, United States

Location

MeSH Terms

Conditions

Keratosis, Actinic

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Head of Global Clinical Development
• Organization: Almirall S.A.

rd@almirall.com

+34932913000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 15, 2022
• Study Start: June 28, 2022
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: January 23, 2024
• Results First Posted: January 23, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)